Patterns of central nervous system and leptomeningeal involvement in advanced breast cancer with invasive lobular histology: a large multicenter study with a focus on estrogen receptor-positive/HER2-negative disease

@article{miglietta2026patterns,
  title = {{Patterns of central nervous system and leptomeningeal involvement in advanced breast cancer with invasive lobular histology: a large multicenter study with a focus on estrogen receptor-positive/HER2-negative disease}},
  author = {F. Miglietta and C. Vernieri and T. Giarratano and G. Griguolo and M. Bottosso and A. Vingiani and F. Piacentini and M. Cacciatore and A. Botticelli and G. Fotia and P. Napolitano and G. Landa and G.M. Vernaci and E. Di Liso and L. Casadei and D. Palleschi and G. Pruneri and A.P. Dei Tos and V. Guarneri and M.V. Dieci},
  journal = {ESMO open},
  year = {2026},
  month = oct,
  doi = {10.1016/j.esmoop.2026.108550},
  url = {https://europepmc.org/article/PMC/PMC13718780},
  note = {CC BY-NC-ND},
}

TY  - JOUR
TI  - Patterns of central nervous system and leptomeningeal involvement in advanced breast cancer with invasive lobular histology: a large multicenter study with a focus on estrogen receptor-positive/HER2-negative disease
AU  - F. Miglietta
AU  - C. Vernieri
AU  - T. Giarratano
AU  - G. Griguolo
AU  - M. Bottosso
AU  - A. Vingiani
AU  - F. Piacentini
AU  - M. Cacciatore
AU  - A. Botticelli
AU  - G. Fotia
AU  - P. Napolitano
AU  - G. Landa
AU  - G.M. Vernaci
AU  - E. Di Liso
AU  - L. Casadei
AU  - D. Palleschi
AU  - G. Pruneri
AU  - A.P. Dei Tos
AU  - V. Guarneri
AU  - M.V. Dieci
PY  - 2026
DA  - 2026/10/21
JO  - ESMO open
DO  - 10.1016/j.esmoop.2026.108550
UR  - https://europepmc.org/article/PMC/PMC13718780
AB  - Background: Invasive lobular carcinoma (ILC) is known to exhibit distinct metastatic patterns compared with carcinoma of no special type (NST); however, little is known about its specific propensity for central nervous system (CNS) and leptomeningeal (LM) involvement, particularly in estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative subtype.  Patients and methods: We leveraged a multicenter study of 1710 patients with advanced breast cancer (BC). We recorded site of first metastatic recurrence and occurrence/type of the first CNS event. The study endpoints were CNS-free survival, LM-free survival, and post-LM survival. The risk of LM as the first CNS event across histological types was evaluated using a competing-risk framework.  Results: Among 1587 patients with known tumor histology, 15.5% had ILC. Within the ER-positive/HER2-negative BC cohort (n = 669), 31.5% of patients developed a CNS event. ILC and NST were associated with similar metastatic CNS-free survival [hazard ratio (HR) 1.30, 95% confidence interval (CI) 0.95-1.77, P = 0.095]. In contrast, metastatic LM-free survival was significantly and independently shorter in ILC versus NST (multivariate analysis of LM events without concurrent brain metastases, adjusted HR 4.94, 95% CI 1.57-15.83, P = 0.006). Consistently, Fine-Gray competing-risk analysis confirmed a significantly higher risk of LM involvement as the first CNS event for ILC versus NST (adjusted subdistribution hazard ratio 5.07, 95% CI 1.57-16.41, P = 0.007). Among patients with ER-positive/HER2-negative BC and LM disease, ILC was associated with worse post-LM survival compared with NST (HR 2.79, 95% CI 1.03-4.17, P = 0.040). In patients with ILC presenting with extracranial metastatic disease, we observed similar LM-free survival between those treated with cyclin-dependent kinase 4 and 6 inhibitors and those who were not (P = 0.286).  Conclusions: In patients with ER-positive/HER2-negative advanced BC, ILC was independently associated with a higher cumulative incidence of LM as the first CNS event than NST. Patients with ILC who developed LM also experienced poorer post-LM survival. These findings highlight the need for heightened clinical awareness and support prospective studies evaluating earlier LM detection in this population.
SN  - 2059-7029
ER  -